Fungicidal compositions



United States Patent 2,785,102 FUNGICIDAL COMPOSITIONS Waldo B. Ligett,Pontiac, and Rex D. Closson, Detroit, Mich, and Calvin N. Wolf, NewYork, N. Y., assignors to Ethyl Corporation, New York, N. Y., acorporation of Delaware No Drawing. Application March 25, 1954, SerialNo. 418,770

4 Claims. (Cl. 167-33) This invention relates to substitutedsuccinhydrazides. In particular our invention relates to a class ofcompounds which have utility as fungitoxicants, methods of formulatingsuch compounds into useful fungicides, and methods of their application.This application is a continuation-in-part of our copending applicationSerial Number 350,772, now abandoned, which in turn is acontinuation-in-part of our copending application Serial Number 192,806,filed October 28, 1950, which has now matured into U. S. Patent2,640,005.

The compounds comprising the active ingredients of the formulations ofour invention comprise the class of monoand di-substituted1,2,4,5-tetrahydropyridazine- 3,6-diones and are characterized by beingpotent biocides,

being particularly effective against fungus organisms.

wherein the substituents X and Y are the same or dif-' ferent and areselected from hydrogen and negative radicals, but not more than one of Xor Y is hydrogen. Among the negative radicals which comprise certainembodiments of the novel compounds of our invention we include thesulfhydryl group (4H), mercaptans (-SR), the trichloromethylthio(-SCCLs) group, alkyland aryloxy, acyloxy and aroyloxy (RCOO-),''nitroso, 'nitro, amino, and monoand di-substituted amino.

Correct nomenclature for the compounds of this invention requires thatthey be referred to as derivatives of1,2,4,5-tet1ahydropyridazine-3,6-dione, wherein one or more substituentsare substituted in the 4-, or 4,5-positions, that is, at least one ofthe methylene groups is substituted. However, for the sake of brevity wecan refer to the compounds of our invention as substitutedsuccinhydrazides. Thus, our compounds are referred to as a-, and cd-substituted succinhydrazides.

The compounds of this invention are solids of fairly high melting point,usually above 50 C. They contain carbon, hydrogen, oxygen, nitrogen, andin some cases sulfur and halogen atoms. They are somewhat acid in natureand form salts with strong alkali. They tend to hydrolyze on contactwith water, particularly on prolonged contact at higher temperatures.With certain substituents on the methylene carbon atoms, such as theamino radical, this acidity is counteracted to some extent by thealkalinity of the substituent group. The compounds of this invention arequite reactive and undergo a variety of chemical reactions.

One method of synthesizing the substituted succinhydrazides of thisinvention comprises treating hydrazine or hydrazine hydrate with theanhydride of the appropriately substituted succinic acid. Reactionproceeds readily in most cases, and requires the use of a solvent tomoderatethe exothermic reaction.

The following examples, wherein all parts and per centages are on theweight basis, describe the preparation of typical new compounds of thepresent invention.

Example I hour. After cooling to room temperature, the solid prod net isfiltered and washed with benzene. This product,

a-mercaptosuccinic hydrazide, is obtained in high yield and has theempirical formula C4H502N2S.

Example II The procedure of Example I is repeated usinga-methylmercaptosuccinic anhydride as the reactant.a-methylmercaptosuccinic hydrazide corresponding to the formula C5H7O2N2is obtained in high yield.

Example III Using the procedure of Example I witha-trichloromethylthiosuccinic anhydride as a reactant, a good yield ofa-trichloromethylthiosuccinic hydrazide is obtained.

Example IV a-Propionylsuccinic anhydride is converted toa-propionylsuccinic hydrazide in high yield and high purity' by theprocedure of Example 1.

Example V By the procedure of Example I, the following succinichydrazides are prepared by reaction of the corresponding" succinicanhydride and hydrazine hydrate:

- a-Benzoylsuccinic hydrazide a-Acetoxysuccinic hydrazidea-p-Tolyloxysuccinic hydrazide a-Nitrososuccinic hydrazidea-Nitrosuccinic hydrazide a-Aminosuccinic hydrazidea-Methylaminosuccinic hydrazide a-Dimethylaminosuccinic hydrazidea-Mercapto-a-trichloromethylthiosuccinic hydrazidea-Amino-a'-nitrosuccinic hydrazide a-Acetyl-a-benzoylsuccinic hydrazideA wide variety of radicals can be substituted in thel,2,4,5-tetrahydropyridazine-3,6-dione structure to produce materialsuseful as fungicidal agents. Useful embodiments of our novel compoundscomprise those in which one or more sulfur-containinggroups are in the4- or 5- or 4,5-positions. Such sulfur-containing groups include, forexample, the sulfhydryl group, the trichloromethylthio group, andsubstituted mercapto group, wherein R is alkyl, such as, for example,methyl, ethyl, propyl, n-butyl, i-butyl, amyl, hexyl, dodecyl, benzyl,or phenylethyl or aryl or substituted aryl, typical examples of whichare phenyl, tolyl, xylyl, and naphthyl.

Further typical examples of substituent groups which can be substitutedin the 4-, 5-, or 4,5-positions of the compounds of our novelformulations comprise alkoxy, aryloxy, and acyloxy and aroyloxy groups.Typical examples of alkoxy groups which we employ comprise methoxy,ethoxy, propoxy, isopropoxy, allyloxy, 2'-methylhexoxy, fi-chloroethoxy,fi-aminoethoxy, and benzyloxy. As aryloxy substituents we can employsuch typical groups as phenoxy, 4-isopropylphenoxy, 2',4-dichloro- Themixture is stirred for one hour phenoxy and 3'-nitropl1enoxy. Among theacyloxy and W aroyloxy groups we can employ in the 4-, 5-, or 4,5-positions of our l,2,4,5-tetrahydropyridazine-3,6-diones, representativemembers include acetoxy, mono-, di-, and trichloroacetoxy, .propionoxy,lau'r oyloxy, etol-uyloxy; benzoyloxy, toluyloxy,anisoyloxy,anthnanoyloxy, 4"-c1-. 1e'- robenzoyloxy, and2'-.hydroxybenzyloxy,'and the like.

Among nitrogen containing groups which we can substitute inthe be, 06-,.or e d-positions of our succinhydrazides, typical examples include thenitroso, nitro, and amino groups. The amino groups can be unsubstitutedor can comprise the, monoand dialkyl and aryl or aryl alkyl amines.rIllustrative of such amine ,groups are methylamino, ethylamino,'hexylamino, N emethyl IN- ethylamino, isopropylamino, cyclohexylamino,"Z methylhexylamino, lfiehydroxyethylamino, aniline, N-phenyl-N-methylamino, piperidyl, morpholino, rand pyri'dyl.

It is'understood that mixtures of the negative radicals of the compoundsof our invention can be co-substituted in many variations andcombinations on the av, oL', or d,d'-POSitiOHS of the succinhydrazides.

Substituted succinic anhydrides can be condensed with hydrazine hydrateaccording to the procedure of the foregoing examples to produce thesuccinhydrazides of the formulations of our invention. Thus, forexample,

when each of oc-nitl'O, oc-fiHOI'0-a'-Dlt-I'O-, rx-mercapto-.,a-tn'chloromethylthio-, a-methoxy-M-nitro, a,a-'diacetoxy-,u-anilino-a-iodo-, a-nitr0S0a'-Chl0IO-, a-methylmercapto-,a-(N-methyl-N-butylamino) m'-nitro-, oz-ChlOIO- a-butenyl-,a-cyclohexyl-a-acetoxy-, and a-aminosuccinic anhydride is treated inbenzene or an alcohol solution with a solution of hydrazine hydrate inethyl alcohol, there is obtained, respectively, a-nitr oa-fiuoro-a'-nitro'-, a-mercapto-, u-trichloromethylthio-,a-methoxy-a'-nitro, a,a'-diacetoxy-, a-anilino a iodo-,a-nitroso-u-chloro-, a-methylmercapto-,a-(N-methyl-N-butylaminoya-nitro-, oc-ChlOIO a butenyl-, a-cyclohexyl aacetoxy-, and a-aminosuccinhydrazide. f

The compounds of our invention can be employed as fungicides and for theprevention of the germination of the spores of fungi. To demonstrate theutility of'lthe succinhydrazides of our invention as fungicidalcompositions, we determined the concentration at which the'germinationof 50 percent of the spores of each ofthe fungi Alternaria oleracea andSclerotz'nia fiucticolrz isinhibited. The former is responsible for thepotato blight, while the latter causes peach rot. These fungi arerepresentative of fungus types which are responsible for heavy cropdamage. The ability to control these fungi is. a reliableindication ofthe general applicability of our fungicides toprotect these and otherimportant agricultural crops. These tests were conducted. as follows:100 parts of the active ingredient was triturated with 1,000 parts ofdistilled water containing one part of the commercial dispersant TritonX-100. This standard suspension was thereupon further diluted withdistilled water, and the concentration at which one-half of the fungicontained'in a drop of water on a microscope slide wereprevented fromsporulating was determined. When 'thefollowing typical examples of thecompounds of our invention are so applied to cultures of these fungi,they are 'eflective at low concentration: a amino-, mtrichloromethylthio-, a nitro zx' chloro-, a-butylmercapto-,a-methylamino cc nitro-, .a-nitroso-, '-mercapto'-, anda,a'-diacetoxysuccinhydrazide.

Other examples of the novel class of compounds which we have providedwill .be apparent, those specific examples enumerated herein beingmerely illustrative. Furthermore, other methods for their preparationwill be apparent to those skilled in the art, and the foregoing examplesof preparation are presentedmere'ly'to illustrate one method for theirpreparation.

We claim:

1. As new compositions of matter, 1,2,4,5-tetrah ydrpyridazine-3,'6-diones in which at least one of themethylene groups issubstituted with a-radical selected from-the class consisting ofsulfhydryl, alkyl merc'aptans of -1 to 12 carbon atoms, aryl mercap'tansof 6 to 10 carbon atoms, trichloromethylthio, 'alkyloxy of l to 8 carbonatoms. 7

'2. A process for the manufacture of fungicidal 1,2,4,5-

tetrahydropyridazine-3,6-diones which comprises reacting a memberselected from the group consisting of hydrazine and hydrazine hydratewith a succinic anhydride wherein at least one of the methylene groupsof said succinic anhydride is substituted with a radical of claim 1.

3. A fungicidal composition consisting essentially of the composition ofclaim 1, and a dispersant.

4. The method of treating materials susceptible to fun- P gus attackwith a fungicidal composition containing as the principal activeingredient l,2,4,5-tetrahydropyridazine-3,6-diones in which at least oneof the methylene groups is substituted with a radical selected from theclass consisting of sulfhydryl, a-lk-yl mercaptans of l' to V 12 carbonatoms, arylmercaptans of 6' to 1'0'carbon atoms,

trichlor'omethylthio, and alkyloxy of l to 8 carbon atoms.

Ligett et'al, May 26, 19 53

1. AS NEW COMPOSITION OF MATTER, 1,2,4,5-TETRAHYDROPYRIDAZINE-3,6-DIONESIN WHICH AT LEAST ONE OF THE METHYLENE GROUPS IN SUBSTITUTED WITH ARADICAL SELECTED FROM THE CLASS CONSISTING OF SULFHYDRYL, ALKYLMERCAPTANS OF 1 TO 12 CARBON ATOMS, ARYL MERCAPTANS OF 6 TO 10 CARBONATOMS, TRICHLOROMETHYLTHIO, ALDYLOXY OF 1 TO 8 CARBON ATOMS.
 4. THEMETHOD OF TREATING MATERIAL SUSCEPTIBLE TO FUNGUS ATTACT WITH AFUNGICIDAL COMPOSITION CONTAINING AS THE PRINCIPAL ACTIVE INGREDIENT1,2,4,5-TETRAHYDROPYRIDAZINE-3,6-DIONES IN WHICH AT LEAST ONE OF THEMEHTYLENE GROUPS IS SUBSTITUTED WITH A RADICAL SELECTED FROM THE CLASSCONSISTING OF SULFHYDRYL, ALKYL MERCAPTANS OF 1 TO 12 CARBON ATOMS, ARYLMERCAPTANS OF 6 TO 10 CARBON ATOMS, TRICHLOROMETHYLTHIO, AND ALKYLOXY OF1 TO 8 CARBON ATOMS.